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Clinical Picture
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In DMD, boys often walk at a later age than the average
child and often start to show signs of muscle disease
in toddlerhood. Specific signs of muscle disease may
include problems with balance, trouble climbing the
stairs or trouble standing up from a sitting position.
DMD gradually weakens the skeletal muscles, a type of
voluntary muscle in specific muscle groups (shown to
the right) of the body. BMD is more mild than DMD, with
a later age of onset. The same muscle groups are affected,
however the progression is often slower and less predictable
than what is seen in DMD.
Figure 1: Muscles affected in DMD and BMD (shown in
red):
• Pectoral muscles – the muscles in the chest
which help control the shoulders.
•Trunk muscles – the muscles which help control
our posture and support us.
•Muscles of the upper and lower legs – the
muscles which help us to stand, walk, sit, climb stairs.
Affected boys often have pseudohypertrophy, or enlarged
calf muscles and may appear to be clumsy.
•Of note, some children with DMD have arm weakness
and difficulty raising their arms.
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Figure 1.
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Children with DMD may demonstrate the “Gower’s
maneuver.“ This is a term used to describe the way that
children with leg weakness help themselves to stand up, by
getting on their hands and knees in a crawling position and
then elevating their posterior. They then press their hands
against their legs for support and raise to a standing position.
Generally, when they reach age 4 or 5, they may "toe
walk"and stick out their stomach and put their shoulders
back. This is to compensate for their muscle weakness and
to help them to maintain balance. Most children with DMD can
no longer walk unassisted when they are between the ages of
7 and 12. By early teens, the heart and respiratory muscles
may be affected.
In BMD, symptoms often present when adolescents begin to walk
with a waddling gate, and they protrude their stomach to help
with balance. They then develop weakness in the hips, pelvic
area, thighs and shoulders. Often, individuals with BMD are
in wheelchairs by the time they are in their thirties, or
even later, while others with BMD may maintain the ability
to walk with canes and/or braces for many years.
Other Ways DMD and BMD Affect the Body
In general, the muscle deterioration associated with DMD and
BMD does not cause the affected child to be in pain. However,
some people with these muscular dystrophies report muscle cramps,
which can be easily treated. They may develop a joint condition
called contractures, which means that some of their joints may
become stiff and fixed in one position. Spinal curvatures are
also a potential problem that should be monitored for.
Usually by the time one with DMD becomes a teenager, heart and
respiratory symptoms appear as a result of weakening in the
heart muscles and the muscles that help the lungs to function.
These symptoms can be serious and should be monitored closely.
Ask your physician about the symptoms of heart weakness and
damage and changes in lung function.
Different people have different levels of symptoms of DMD and
BMD. Some people with BMD have only mild skeletal muscle problems
but severe cardiac complications. Further, different people
with muscular dystrophy maintain more muscular function than
others. It is important that patients with BMD and DMD have
thorough physical examinations, including checking the heart,
lungs, cognitive function, and other systems of the body. Modern
medical technology may allow for life-saving or life-lengthening
procedures.
What causes DMD and BMD
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DMD is a genetic neuromuscular condition that occurs
because of a genetic mutation on a gene (the dystrophin
gene) on the X chromosome. In healthy individuals, this
gene codes for the production of a special protein called
dystrophin. However, in DMD, when there is a genetic
change in this gene, it causes the gene to not make
this protein. Dystrophin is a unique protein under the
cell membrane in a muscle cell that keeps the muscle
cell working properly. BMD results from different genetic
alterations in the same gene on the X chromosome. The
mutations in BMD allow some of the protein to be made.
In BMD, the small amount of dystrophin protein that
is made is of low quantity or of too poor quality to
function properly. However, the presence of some dystrophin
reduces the severity of the muscular dystrophy and often
symptoms appear at a later age than DMD.
Figure 2: Human skeletal muscles are made up of special
cells (myofibers) that are surrounded by a membrane
(called the sarcolemma) and are arranged in bundles.
Several proteins surround each muscle fiber along the
membrane and are essential for our muscle cells to function
normally. These proteins work together, and when one
of them is absent or malfunctioning, often the result
is muscular dystrophy. For a more thorough review of
muscle, please refer to our Muscle
Anatomy Review section.
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Figure 2.
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As you may recall, the mutation causing DMD and BMD is located
on the X chromosome. Every healthy person has 46 chromosomes
(or 23 pair of chromosomes) in most cells of the body. Twenty-three
chromosomes are inherited from the egg of a mother, and 23
are inherited from the sperm of the father. The twenty-third
pair of chromosomes is called the sex chromosomes and is represented
by an X or a Y. Males inherit an X chromosome from their mother,
and a Y chromosome from their father. Females get one X chromosome
from each parent. A woman is a carrier of DMD or BMD if she
carries a mutation in the dystrophin gene on one of her X
chromosomes. If a woman is a carrier, each son that she bears
has a 50% chance of inheriting the altered gene and having
DMD or BMD. For a female carrier, each of her daughters has
a 50% chance of inheriting the mutation and being a carrier.
Carriers generally do not have symptoms of the muscular dystrophy,
but are at risk for passing on the dystrophin mutation to
their children.
Ways a person gets DMD or BMD:
There are three main ways that an individual can get these disorders.
- A mother with an alteration in the dystrophin gene on
one of her two X chromosomes passed on the gene to her son.
(This occurs in approximately 2/3 of the cases.) A man with
DMD or BMD can’t pass on an altered gene to his sons
because he gives a son a Y chromosome. A man can pass on
the altered gene to his daughters, because a daughter inherits
an X chromosome from her father. This would make the daughter
a carrier. However, males with DMD generally do not pass
on a dystrophin gene mutation because they often do not
reach the age or level of health necessary to have children.
- A genetic alteration occurred in the sperm or egg that
formed the embryo by chance. This is called a sporadic mutation
and occurs in approximately 1/3 of the cases. If this occurs,
then other family members other than the affected person’s
children are not at increased risk to get DMD or BMD. Children
with a parent with sporadic DMD/BMD have a 50% chance of
inheriting DMD/BMD.
- A parent has germline mosaicism, a very rare genetic phenomenon.
This means that not all the cells in a person’s body
have the same genetic content. Germline refers to the sex
cells that form eggs in women and sperm in men. Mosaicism
is an event that happens when a new mutation occurs in a
single cell early in the pregnancy when the baby is a tiny
embryo. This cell then divides over and over, with the mutation
present in all the cells that came from the original cell
with the mutation. Consequently, only some cells in the
person’s body have the DNA with a mutation, and the
other cells do not. The effect of mosaicism varies in every
person. Some mosaic individuals may show no signs of the
disease, but are at risk to pass on DMD/BMD to their children
if their sex cells contain the deletion. Other mosaic individuals
may have a severe case of DMD or BMD. (In 5-15% of cases
of affected sons where the mother is tested and a mutation
cannot be found, germline mosaicism is present.)
It may be that a person is the first in the family to have
DMD or BMD. This can happen if the dystrophin mutation existed
in the females of a family for several generations, but no
one knew it because no children affected with muscular dystrophy
were born. Also, relatives from years past may not have known
what the disease was that a male child had. Last, the child
with DMD or BMD may have a new (sporadic) genetic mutation.
Testing For and Diagnosing Muscular
Dystrophy
The first step in diagnosing muscular dystrophy is noticing
the signs of muscular weakness in your child. Next, a visit
with a physician will include a detailed physical examination
and detailed questions, including asking about the patient and
the family medical histories. The doctor or nurse may ask many
questions about the patient’s siblings, parents, aunts
and uncles, grandparents and cousins and construct a family
tree, which is called a pedigree. A physical examination will
focus on muscle weakness and the nervous system. Additional
studies such as electrical tests of nerve and muscle (electromyogram
or EMG) may be performed. Together, these studies determine
whether the patient’s weakness is a result of problems
with muscles, nerves, spinal cord or brain.
Sometimes doctors will order a special blood test that measures
an enzyme in one’s blood called creatine kinase, or CK.
When muscle is damaged, as in the case of muscular dystrophies,
this enzyme leaks out of the muscle cells and gets into the
blood. A high CK blood level, therefore, suggests that the muscles
are likely the cause of the weakness rather than the nerves.
Further studies will be needed to determine the exact type of
muscle disorder. Carrier mothers may or may not have elevated
serum CKs.
Since there are so many types of muscle diseases, the physician
may order a muscle biopsy to determine which is the specific
cause of a particular patient’s weakness. This biopsy
is a minor surgical procedure that involves removal of a small
piece of muscle (usually through a small incision), typically
in the area of the thigh (quadricep) or upper arm (deltoid).
By examining this sample under the microscope, doctors gain
much information about what is happening in the muscle cells.
This may help distinguish one muscle disorder from another.
Often, the muscle is stained with special dyes to look for
the absence or presence of proteins, such as dystrophin. Finding
that a protein is abnormal (either absent or abnormal in size
and quantity) helps define the genes and proteins that are
likely candidates causing the muscle problems. In the case
of Duchenne muscular dystrophy, we often won’t see any
of the dystrophin protein. However, in Becker muscular dystrophy,
we will see some protein, but a decreased amount from what
is present in individuals without these muscle disorders.
Genetic Testing
There is genetic testing available for DMD/BMD, which takes
on average 2 – 6 weeks for results. Genetic testing is
performed by taking 2 – 6 teaspoons of a patient’s
blood. From the blood, DNA can be isolated and scientists can
read the DNA code in the dystrophin gene to see if any alterations
(mutations) are present. When the DNA is has an alteration in
it, such as a portion that is deleted, the protein that this
gene codes for may be missing or may not function properly,
which leads to muscle weakness. The alterations found in patients
with DMD/BMD are mostly deletions in DNA (60-65% of cases).
The remaining percentage is caused by more subtle changes in
the DNA sequence in the dystrophin gene. It is important for
healthcare providers to remember that it is always most informative
to test an affected individual first for a genetic alteration,
and then proceed to test other family members as necessary.
Genetic testing, although informative in many cases, is still
not perfect. Infrequently, test results may be negative, meaning
no mutation is found. This can mean that a laboratory missed
a subtle mutation (which is a rare event) or that a mutation
actually is not present in the gene. Test results may also be
positive (mutation is found), or uncertain (scientists may be
uncertain of the clinical significance of a certain alteration
in a patient’s DNA). Genetic testing can also be used to
check to see if a mother or female relative is a carrier of
the genetic alteration found in the patient. The cost of the
testing depends on who is doing the testing. Usually the cost
is covered, at least in part, by insurance companies.
The decision to be genetically tested is a very important
and personal decision. It may effect your family life and
family planning, relationships, career and insurance decisions,
and psychological and emotional well-being. It is a decision
to be carefully made and it can have a very positive or a
less positive outcome. Genetic counselors are available to
individuals who are considering genetic testing. Further,
often genetic counselors can put families in touch with other
families who are going through similar situations. Genetic
counseling provides useful information about the implications
of the testing and emotional support by someone with special
training and expertise in the field. Genetic counselors also
provide information on prenatal testing for DMD/BMD to see
if an unborn baby has inherited a genetic mutation. This testing
can be done if there is an affected relative in the family
or if the mother is known to be a carrier of a genetic alteration
in the dystrophin gene. Genetic counselors also can provide
information on alternative methods of reproduction, such as
adoption and preimplantation diagnosis (PGD). In PGD, eggs
are obtained from the mother that are then fertilized by the
father’s sperm in a laboratory. Genetic testing is then
done on the embryos to test for DMD/BMD. Only those embryos
that have not inherited the mutation for DMD/BMD are implanted
into the mother’s womb. Prenatal testing and PGD are
complex issues and are not covered in depth in this site.
For more information, speak with a physician or a genetic
counselor.
Treatment of DMD and BMD
Muscle strength is responsible for every voluntary movement
an individual makes. Muscles work with our bones to hold or
support the bones in the proper place and to control movement.
When muscles weaken, bone or joint problems may result. This
can be seen in DMD and BMD when affected individuals develop
joint problems or spine problems. There is treatment for these
problems, such as excersizes and assistive devises (braces and
positioning aids) that can help people with DMD or BMD.
As muscle deteriorates, a person with DMD or BMD often develop
contractures, which are fixations of the joints (knees, hips,
feet, elbows, wrists, and fingers). If left untreated, contractures
can become severe and cause discomfort and restricted mobility.
However, contractures can be treated with the help of a physical
therapist, braces, and in severe cases, by surgery.
Because the spine can be gradually pulled into a curved shape
from muscular weakening, spinal curvatures are a risk for
boys affected with muscular dystrophy. There are different
types of spinal curvatures:
•scoliosis - a curve from side to side
•kyphosis - forward “hunchback” curve
•lordosis - a backward curvature in the spine, whereby
individuals walk sway-back
Severe scoliosis can be problematic if it interferes with
daily functions, such as sitting, sleeping, and breathing.
Thus, it is best if it is prevented or treated promptly if
it is diagnosed with a brace or spinal surgery.
Unfortunately, there is no cure for muscular dystrophy and
there are no ways to stop or fix the muscle weakening and
degeneration that is a result of DMD or BMD. However, there
are medications that can be taken to slow down the degeneration
process. One such medication is a catabolic steroid called
prednisone. This drug may slow the loss of muscle weakness
or possibly increase strength in patients with DMD, thus preserving
independent walking temporarily. Like many medications, however,
prednisone has potentially damaging side effects which should
be carefully discussed with a physician prior to administering
the medication to your child.
At some point, every child with DMD and most men with BMD
will require a wheelchair. Generally, by age 12, children
with DMD need to use a wheelchair full-time. In BMD, this
usually occurs in the third decade of life or later. Often,
the person with DMD or BMD and their family see the wheelchair
as a sign of disability and want to postpone using it. However,
most users and their families are grateful for the wheelchair
and find that life is easier because they can remain more
independent and energetic by using the chair.
We are grateful that many medical advances through the years
have lead to numerous therapies that are available to help
children with DMD and BMD. There are many specialists available
that can help with caring for a child with muscular dystrophy.
Contact the Muscular Dystrophy Association for information
on a clinic or physician near you.
Support
After one is confirmed to have muscular dystrophy, one may experience
overwhelming thoughts and emotions. There are several sources
of support the patient or the family members of the patient
can seek. Please use the links below to view support group and
educational information that could benefit a person with muscular
dystrophy or a family member of a person with muscular dystrophy.
Research
As more people participate in research for muscular dystrophy,
our knowledge of the mechanisms that cause these disorders will
improve. As our understanding of the disorders increases, we
will be better able to treat and manage these conditions. There
is research being done on muscular dystrophy and related muscular
disorders. Please visit Our
Research find out more about the research being done and
to stay informed about new advances.
Links Page
Muscular Dystrophy Association
www.mdausa.org
Muscular Dystrophy Campaign
www.muscular-dystrophy.org
Duchenne Parent Project
www.parentdmd.org
The Muscular Dystrophy Family Foundation
www.mdff.org
The Foundation for Gene and Cell Therapy: Jesse's
Journey
www.jessesjourney.com
To find a genetic counselor near you, please visit the National
Society of Genetic Counselors Web site.
Some content adapted from the Muscular
Dystrophy Association. For more detailed information, visit
the MDA web site at www.mdausa.org
Figures 1 and 2: Graphics used with permission of the
Muscular Dystrophy Association.
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